1. Field of the Invention
The present invention relates to antibodies, pharmaceutical compositions and methods for increasing all isoforms of sodium potassium ATPase activity in a cell, tissue, organ, or bodily fluid. It also relates to the use of the antibodies and pharmaceutical compositions to treat or prevent diseases associated with low NKA activity in an animal.
2. Description of the Related Art
Sodium potassium ATPase (hereafter referred to as “NKA”) [1] is an integral membrane protein that couples the hydrolysis of ATP to the vectorial transport of Na+ ions and K+ ions across the plasma membrane of all animal cells 121. The overall stoichiometry of the reaction is three Na+ ions transported out of the cell and two K+ ions into the cell for each ATP hydrolyzed. It has been demonstrated that intact NKA is composed of two subunits and only the α-subunit (˜113 kDa) is responsible for the catalytic activity of the enzyme. The smaller β-subunit (˜35 kDa glycoprotein) is necessary for the folding of the complex [3]. Recent transmembrane investigations have suggested that the catalytic α-subunit traverses the membrane ten times and both the N- and C-terminals of the α-subunit are located on the cytoplasmic side [4, 5]. The β-subunit contains one hydrophobic region and only the N-terminal is located on the cytoplasmic side [5, 6]. Several isoforms of both α- and β-subunits have been identified [7]. There are two α isoforms (α1 and α2) on NKA in rodent heart [8, 9] and three α isoforms (α1, α2, and α3) in human heart [10, 11]. All isoforms of NKA share the same catalytic function.
Although extensive studies have been made towards understanding the structure/function relationship of NKA and its central role in biology and medicine, little is known about the activation of NKA and its biological influences. Enzymatic activity of NKA is essential to living cells and continuity of life. However, in certain diseases including heart diseases, liver diseases, lung diseases, Alzheimer's disease, nervous system diseases, intestinal diseases, cataracts and blood diseases. NKA activity is depressed. In the fifty years since the discovery of NKA, there have been no drugs or compounds identified that selectively activate NKA activity.
The past approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, the approaches described in this section are not to be considered prior art to the claims in this application merely due to the presence of these approaches in this background section.